Methods of treating circadian rhythm disorders

Abstract

A method for treating circadian rhythm disorders is described. The method involves the administration of melatonin from about 6 hours to about 19 hours prior to when the normal sleep phase should begin, depending on whether a phase advance shift in circadian rhythms or a phase delay shift is desired. This is typically from about 4 hours to about 17 hours prior to the time of endogenous melatonin onset.

We claim: 
     
       1. A method for achieving a phase-shifting effect in a human having a free-running circadian rhythm that is out of synchrony with the external environment, the method comprising administering melatonin to the human at a time prior to an individual human's endogenous melatonin onset time, the amount of melatonin administered being sufficient to achieve a phase-shifting effect in the human, said amount being less than 1 mg. 
     
     
       2. The method of claim 1 wherein the human is blind. 
     
     
       3. The method of claim 1 wherein human is an infant. 
     
     
       4. The method of claims 1, 2 or 3 wherein the phase-shifting effect is a phase advance and melatonin is administered at about 4 hours to about 8 hours prior to the human's endogenous melatonin onset time. 
     
     
       5. The method of claim 4 wherein melatonin is administered at about 6 hours prior to the human's endogenous melatonin onset time. 
     
     
       6. The method of claim 4 wherein melatonin is administered at about circadian time (CT) 8. 
     
     
       7. The method of claim 4 wherein melatonin is administered at about 8 hours prior to the human's desired sleep onset time. 
     
     
       8. The method of claim 4 wherein melatonin is administered at about 8 hours after the human's sleep offset time. 
     
     
       9. The method of claims 1, 2 or 3 wherein the phase-shifting effect is a phase delay and melatonin is administered at about 12 hours to about 16 hours prior to the human's endogenous melatonin onset time. 
     
     
       10. The method of claim 9 wherein melatonin is administered at about 14 hours prior to the human's endogenous melatonin onset time. 
     
     
       11. The method of claim 9 wherein melatonin is administered at about circadian time (CT) 0. 
     
     
       12. The method of claim 9 wherein melatonin is administered at about 16 hours prior to the human's desired sleep onset time. 
     
     
       13. The method of claim 9 wherein melatonin is administered at the human's sleep offset time. 
     
     
       14. The method of claim 1, wherein melatonin is administered in a multiplicity of doses and administered at different times, wherein the total administered dose is less than about 1 mg, and the dose is administered over a period of about 1 to about 4 hours. 
     
     
       15. The method of claim 14, wherein melatonin is administered in two equal doses. 
     
     
       16. The method of claim 15, wherein the melatonin administration times are separated by less than about 1 hour. 
     
     
       17. The method of claim 15, wherein the earlier of the melatonin administration times is about 8 hours prior to the human's desired sleep onset time. 
     
     
       18. The method of claim 15, wherein the earlier of the melatonin administration times is about 8 hours after the human's sleep offset time. 
     
     
       19. The method of claim 15, whereto the earlier of the melatonin administration times is about 16 hours prior to the human's desired sleep onset time. 
     
     
       20. The method of claim 15, wherein the earlier of the melatonin administration times is about the human's sleep offset time. 
     
     
       21. The method of claims 1, 2 or 3, wherein the circadian rhythm phase-shifting effect results in the human's circadian rhythm of sleep and wakefulness having a period of about 24 hours. 
     
     
       22. The method of claims 1, 2 or 3, wherein the circadian rhythm phase-shifting effect results in a partial entrainment of the human's circadian rhythm of sleep and wakefulness, thereby increasing the proportion of time that said circadian rhythm has a period of about 24 hours. 
     
     
       23. A method for achieving a phase-shifting effect in a human infant comprising the following steps: a) determining the time of the infant's endogenous melatonin onset; and   b) administering an amount of melatonin to the infant in milk at a specific time prior to the infant's endogenous melatonin onset, the amount of melatonin being sufficient to achieve the phase-shifting effect in the infant, said amount being less than 1 mg.   
     
     
       24. The method of claim 23 wherein the phase-shifting effect is a phase advance and the melatonin is administered at about 4 hours to about 8 hours prior to the infant's endogenous melatonin onset. 
     
     
       25. The method of claim 23 wherein the phase-shifting effect is a phase delay and the melatonin is administered at about 9 hours to about 12 hours prior to the infant's endogenous melatonin onset. 
     
     
       26. A method for achieving a phase-shifting effect in a blind human comprising the following steps: a) determining the time of the blind human's endogenous melatonin onset; and   b) administering an amount of melatonin to the blind human at a specific time each day prior to the blind human's endogenous melatonin onset, the amount of melatonin being sufficient to achieve the phase-shifting effect in the human, said amount being less than 1 mg.   
     
     
       27. The method of 26 wherein the phase-shifting effect is a phase advance and the melatonin is administered at about 4 hours to about 8 hours prior to the human's endogenous melatonin onset. 
     
     
       28. The method of claim 26 wherein the phase-shifting effect is a phase delay and the melatonin is administered at about 6 hours to about 19 hours prior to the human's endogenous melatonin onset.